B-Cell Lymphoma Originating in the CNS Clinical Trial
— DRBEATOfficial title:
A Phase 2a Study of the Addition of Temozolomide to a Standard Conditioning Regimen for Autologous Stem Cell Transplantation in Relapsed and Refractory Central Nervous System (CNS) Lymphoma
| Verified date | October 2018 |
| Source | Cedars-Sinai Medical Center |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The primary purpose of the study will be testing the dosing of temozolomide to find the
target dose that a person can tolerate. The other part of the study will be determining how
helpful it can be to CNS lymphoma patients by adding temozolomide to the "conditioning
regimen" prior to stem cell transplantation.
This research study is designed to test the investigational use of temozolomide as part of a
conditioning regimen prior to stem cell transplantation. This drug has not yet been approved
by the U.S. Food and Drug Administration (FDA) to be used in the setting of stem cell
transplantation in lymphomas of the brain (central nervous system or CNS) but it has been
studied and used before in transplantation with reasonable results.
| Status | Terminated |
| Enrollment | 11 |
| Est. completion date | April 18, 2018 |
| Est. primary completion date | July 28, 2017 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 75 Years |
| Eligibility |
Inclusion Criteria: 1. Patients = 18 years of age and = 75 years of age 2. Patients must have Central Nervous System (CNS) involvement with a mature B-cell non-Hodgkin's Lymphoma, (WHO criteria) 3. Patients must meet one of the below criteria: - Patients who have achieved a complete response (CR) or partial response (PR) after initial therapy for Central Nervous System (CNS) B-cell lymphoma, OR - Patients with relapsed or progressed disease following therapy for CNS B-cell lymphoma who has achieved a subsequent CR or PR following salvage chemotherapy, OR - Patients who are initially refractory to therapy for CNS B-cell lymphoma but who have achieved a CR or PR following a salvage chemotherapy regimen, OR - Patients who have developed CNS relapse from systemic B-cell Non-Hodgkin's lymphoma, and have evidence of chemotherapy sensitive lymphoma. 4. Patients fit for autologous stem cell transplantation 5. Patients able to understand and willing to sign a written informed consent document Exclusion Criteria: 1. Patients whose life expectancy is severely limited by diseases other than malignancy 2. Karnofsky Performance Score <60 3. Patients who are pregnant or breastfeeding 4. Patients who are HIV seropositive 5. Patients who have an uncontrolled infection (presumed or documented) with progression after appropriate therapy for greater than one month 6. Patients with symptomatic coronary artery disease, uncontrolled congestive heart failure. Left Ventricular Ejection Fraction is not required to be measured, however if it is measured, patient is excluded if ejection fraction is <30% 7. Patients requiring supplementary continuous oxygen. DLCO is not required to be measured, however if it is measured, patient is excluded if DLCO <35%. 8. Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function and histology, and for the degree of portal hypertension. Patients with any of the following liver function abnormalities will be excluded 1. Fulminant liver failure 2. Cirrhosis with evidence of portal hypertension or bridging fibrosis 3. Alcoholic hepatitis 4. Esophageal varices 5. A history of bleeding esophageal varices 6. Hepatic encephalopathy 7. Uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time 8. Ascites related to portal hypertension 9. Chronic viral hepatitis with total serum bilirubin >3 mg/dL 10. Symptomatic biliary disease 9. Patients with non-B-cell lymphomas or brain tumors that are not lymphomas are Excluded from the study. Non-B-cell lymphomas include: any T-cell lymphoma, natural killer (NK)-cell lymphomas, and Hodgkin lymphomas 10. Patients for whom an insufficient number of stem cells (<2 X 106/kg) have been collected |
| Country | Name | City | State |
|---|---|---|---|
| United States | Cedars Sinai Medical Center | Los Angeles | California |
| Lead Sponsor | Collaborator |
|---|---|
| Cedars-Sinai Medical Center |
United States,
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| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | One-year Progression-free Survival and Overall Survival | Efficacy of the DRBEAT Regimen will be assessed by analysis of one-year progression-free survival (PFS), defined as the time interval from maximal response from therapy to tumor regrowth, progression*, or death, (*Progression is defined as meeting the response criteria listed in Table 4: Response Criteria for Primary Central Nervous System Lymphoma according to Abrey LE, Batchelor TT, Ferreri AJM et al.) and Overall survival, defined as the time interval between the date of transplant and the date of death from any cause. |
(1) One Year (2) Until date of death from any cause, assessed up to 2 years | |
| Primary | Safest Dose of Temozolomide for the DRBEAT Regimen | Safety will be assessed using a dose escalation design for temozolomide's use to determine the target dose and also to evaluate any and all acute treatment related toxicities. During the course of patient follow up and therapy, toxicities will be evaluated, particularly as the investigators will be determining the target dose of temozolomide. One of the major criteria for dose limiting toxicity for the study will be any Grade 3 or 4 nonhematologic toxicity from a list of commonly expected toxicities associated with autologous transplantation and temozolomide. | One Year |